Biological effects of bergamot and its potential therapeutic use as an anti-inflammatory, antioxidant, and anticancer agent

References

• Adakudugu EA, Ameyaw EO, Obese E, Biney RP, Henneh IT, Aidoo DB, Oge EN, Attah IY, Obiri DD. 2020. Protective effect of bergapten in acetic acid-induced colitis in rats. Heliyon. 6(8):e04710.
   PubMed Web of Science ®Google Scholar
• Adorisio S, Fierabracci A, Rossetto A, Muscari I, Nardicchi V, Liberati AM, Riccardi C, Sung T Van, Thuy TT, Delfino DV. 2016. Integration of traditional and Western medicine in Vietnamese populations: a review of health perceptions and therapies. Nat Prod Commun. 11:1409–1416.
   PubMed Web of Science ®Google Scholar
• Ahmed D, Comte A, Curk F, Costantino G, Luro F, Dereeper A, Mournet P, Froelicher Y, Ollitrault P. 2019. Genotyping by sequencing can reveal the complex mosaic genomes in gene pools resulting from reticulate evolution: a case study in diploid and polyploid Citrus. Ann Bot. 123(7):1231–1251.
   PubMed Web of Science ®Google Scholar
• Bonfigli AR, Protic O, Olivieri F, Montesanto A, Malatesta G, di Pillo R, Antonicelli R. 2020. Effects of a novel nutraceutical combination (BruMeCholTM) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial. Trials. 21(1):616.
   PubMed Web of Science ®Google Scholar
• Bruno A, Pandolfo G, Crucitti M, Cacciola M, Santoro V, Spina E, Zoccali RA, Muscatello MRA. 2017. Low-dose of bergamot-derived polyphenolic fraction (BPF) did not improve metabolic parameters in second generation antipsychotics-treated patients: results from a 60-days open-label study. Front Pharmacol. 8:197.
   PubMed Web of Science ®Google Scholar
• Calabrò F, Focà A, Anzalone B. 1998. Dalla balsamica virtù dell’essenza di bergamotto nelle ferite. [From the balsamic virtue of bergamot essence in wounds.] Italian. Reggio Calabria, Italy. Laruffa Publisher and Distributor.
   Google Scholar
• Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J. 2009. AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity. Nature. 458(7241):1056–1060.
   PubMed Web of Science ®Google Scholar
• Capomolla AS, Janda E, Paone S, Parafati M, Sawicki T, Mollace R, Ragusa S, Mollace V. 2019. Atherogenic index reduction and weight loss in metabolic syndrome patients treated with a novel pectin-enriched formulation of bergamot polyphenols. Nutrients. 11(6):1271.
   PubMed Web of Science ®Google Scholar
• Carresi C, Musolino V, Gliozzi M, Maiuolo J, Mollace R, Nucera S, Maretta A, Sergi D, Muscoli S, Gratteri S, et al. 2018. Anti-oxidant effect of bergamot polyphenolic fraction counteracts doxorubicin-induced cardiomyopathy: role of autophagy and c-kitposCD45negCD31neg cardiac stem cell activation. J Mol Cell Cardiol. 119:10–18.
   PubMed Web of Science ®Google Scholar
• Cautela D, Vella FM, Laratta B. 2019. The effect of processing methods on phytochemical composition in bergamot juice. Foods. 8(10):474.
   PubMed Web of Science ®Google Scholar
• Cicero AFG, Fogacci F, Bove M, Giovannini M, Borghi C. 2019. Three-arm, placebo-controlled, randomized clinical trial evaluating the metabolic effect of a combined nutraceutical containing a bergamot standardized flavonoid extract in dyslipidemic overweight subjects. Phytother Res. 33(8):2094–2101.
   PubMed Web of Science ®Google Scholar
• Delfino DV, Pozzesi N, Pierangeli S, Ayroldi E, Fierabracci A. 2011. Manipulating thymic apoptosis for future therapy of autoimmune diseases. Curr Pharm Des. 17(29):3108–3119.
   PubMed Web of Science ®Google Scholar
• Delle Monache S, Sanità P, Trapasso E, Ursino MR, Dugo P, Russo M, Ferlazzo N, Calapai G, Angelucci A, Navarra M. 2013. Mechanisms inderlying the anti-tumoral effects of Citrus bergamia juice. PLoS One. 8(4):e61484.
   PubMed Web of Science ®Google Scholar
• Dosoky NS, Setzer WN. 2018. Biological activities and safety of Citrus spp. essential oils. Int J Mol Sci. 19(7):1966.
   PubMed Web of Science ®Google Scholar
• Ferlazzo N, Visalli G, Smeriglio A, Cirmi S, Lombardo GE, Campiglia P, di Pietro A, Navarra M. 2015. Flavonoid fraction of orange and bergamot juices protect human lung epithelial cells from hydrogen peroxide-induced oxidative stress. Evid Based Complement Alternat Med. 2015:957031.
   PubMed Web of Science ®Google Scholar
• Ferlazzo N, Cirmi S, Russo M, Trapasso E, Ursino MR, Lombardo GE, Gangemi S, Calapai G, Navarra M. 2016. NF-κB mediates the antiproliferative and proapoptotic effects of bergamot juice in HepG2 cells. Life Sci. 146:81–91.
   PubMed Web of Science ®Google Scholar
• Ferlazzo N, Cirmi S, Maugeri A, Russo C, Lombardo GE, Gangemi S, Calapai G, Mollace V, Navarra M. 2020. Neuroprotective effect of bergamot juice in 6-OHDA-induced sh-sy5y cell death, an in vitro model of Parkinson’s disease. Pharmaceutics. 12(4):326.
   PubMed Web of Science ®Google Scholar
• Ferro Y, Montalcini T, Mazza E, Foti D, Angotti E, Gliozzi M, Nucera S, Paone S, Bombardelli E, Aversa I, et al. 2020. Randomized clinical trial: bergamot Citrus and wild cardoon reduce liver steatosis and body weight in non-diabetic individuals aged over 50 years. Front Endocrinol. 11:494.
   PubMed Web of Science ®Google Scholar
• Fiorillo M, Peiris-Pagès M, Sanchez-Alvarez R, Bartella L, di Donna L, Dolce V, Sindona G, Sotgia F, Cappello AR, Lisanti MP. 2018. Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism. Biochim Biophys Acta Bioenerg. 1859(9):984–996.
   PubMed Web of Science ®Google Scholar
• Flückiger FA, Hanbury D. 1879. Pharmacographia: a history of the principal drugs of vegetable origin met with in Great Britain and British India. London: Cambridge University Press.
   Google Scholar
• Formisano C, Rigano D, Lopatriello A, Sirignano C, Ramaschi G, Arnoldi L, Riva A, Sardone N, Taglialatela-Scafati O. 2019. Detailed phytochemical characterization of bergamot polyphenolic fraction (BPF) by UPLC-DAD-MS and LC-NMR. J Agric Food Chem. 67(11):3159–3167.
   PubMed Web of Science ®Google Scholar
• Gandhi GR, Vasconcelos ABS, Haran GH, Calisto VdS, Jothi G, Quintans JdS, Cuevas LE, Narain N, Júnior LJQ, Cipolotti R, et al. 2020. Essential oils and its bioactive compounds modulating cytokines: a systematic review on anti-asthmatic and immunomodulatory properties. Phytomedicine. 73:152854.
   PubMed Web of Science ®Google Scholar
• Gattuso G, Caristi C, Gargiulli C, Bellocco E, Toscano G, Leuzzi U. 2006. Flavonoid glycosides in bergamot juice (Citrus bergamia Risso). J Agric Food Chem. 54(11):3929–3935.
   PubMed Web of Science ®Google Scholar
• Giuffrè AM. 2019. Bergamot (Citrus bergamia, Risso): the effects of cultivar and harvest date on functional properties of juice and cloudy juice. Antioxidants. 8(7):221.
   Web of Science ®Google Scholar
• González-Mas MC, Rambla JL, López-Gresa MP, Amparo Blázquez M, Granell A. 2019. Volatile compounds in Citrus essential oils: a comprehensive review. Front Plant Sci. 10:12.
   PubMed Web of Science ®Google Scholar
• Gugliandolo E, Fusco R, D'Amico R, Peditto M, Oteri G, Di Paola R, Cuzzocrea S, Navarra M. 2018. Treatment with a flavonoid-rich fraction of bergamot juice improved lipopolysaccharide-induced periodontitis in rats. Front Pharmacol. 9:1563.
   PubMed Web of Science ®Google Scholar
• Karaca M, Özbek H, Him A, Tütüncü M, Akkan HA, Kaplanoğlu V. 2007. Investigation of anti-inflammatory activity of bergamot oil. Electron J Gen Med. 4(4):176–179.
   Google Scholar
• Marchese E, D'onofrio N, Balestrieri ML, Castaldo D, Ferrari G, Donsì F. 2020. Bergamot essential oil nanoemulsions: antimicrobial and cytotoxic activity. Z Naturforsch C J Biosci. 75(7-8):279–290.
   PubMed Web of Science ®Google Scholar
• Maruca G, Laghetti G, Mafrica R, Turiano D, Hammer K. 2017. The fascinating history of bergamot (Citrus bergamia Risso & Poiteau), the exclusive essence of Calabria: a review. J. Environ. Health Sci A. 6:22–30.
   Google Scholar
• Maugeri A, Ferlazzo N, de Luca L, Gitto R, Navarra M. 2019. The link between the AMPK/SIRT1 axis and a flavonoid-rich extract of Citrus bergamia juice: a cell-free, in silico, and in vitro study. Phytother Res. 33(7):1805–1814.
   PubMed Web of Science ®Google Scholar
• Mazzei R, Leonti M, Spadafora S, Patitucci A, Tagarelli G. 2020. A review of the antimicrobial potential of herbal drugs used in popular Italian medicine (1850s–1950s) to treat bacterial skin diseases. J Ethnopharmacol. 250:112443.
   PubMed Web of Science ®Google Scholar
• Mollace V, Scicchitano M, Paone S, Casale F, Calandruccio C, Gliozzi M, Musolino V, Carresi C, Maiuolo J, Nucera S, et al. 2019. Hypoglycemic and hypolipemic effects of a new lecithin formulation of bergamot polyphenolic fraction: a double blind, randomized, placebo- controlled study. Endocr Metab Immune Disord Drug Targets. 19(2):136–143.
   PubMed Web of Science ®Google Scholar
• Mondello L, Verzera A, Previti P, Crispo F, Dugo G. 1998. Multidimensional capillary GC-GC for the analysis of complex samples. 5. Enantiomeric distribution of monoterpene hydrocarbons, monoterpene alcohols, and linalyl acetate of bergamot (Citrus bergamia Risso et Poiteau) oils. J Agric Food Chem. 46(10):4275–4282.
   Web of Science ®Google Scholar
• Muscari I, Adorisio S, Liberati AM, Thuy TT, Sung TV, Cannarile L, Ayroldi E, Riccardi C, Delfino DV. 2020. BCL-xl overexpression decreases GILZ level and inhibits glucocorticoid-induced activation of caspase-8 and caspase-3 in mouse thymocytes. J Transl Autoimmun. 3:100035.
   PubMedGoogle Scholar
• Navarra M, Ursino MR, Ferlazzo N, Russo M, Schumacher U, Valentiner U. 2014. Effect of Citrus bergamia juice on human neuroblastoma cells in vitro and in metastatic xenograft models. Fitoterapia. 95:83–92.
   PubMed Web of Science ®Google Scholar
• Navarra M, Mannucci C, Delbò M, Calapai G. 2015. Citrus bergamia essential oil: from basic research to clinical application. Front Pharmacol. 6:36.
   PubMed Web of Science ®Google Scholar
• Navarra M, Femia A p, Romagnoli A, Tortora K, Luceri C, Cirmi S, Ferlazzo N, Caderni G. 2020. A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344/NTac-Apcam1137). Eur J Nutr. 59(3):885–894.
   PubMed Web of Science ®Google Scholar
• Peng B, Luo Y, Hu X, Song L, Yang J, Zhu J, Wen Y, Yu R. 2019. Isolation, structural characterization, and immunostimulatory activity of a new water-soluble polysaccharide and its sulfated derivative from Citrus medica L. var. sarcodactylis. Int J Biol Macromol. 123:500–511.
   PubMed Web of Science ®Google Scholar
• Perna S, Spadaccini D, Botteri L, Girometta C, Riva A, Allegrini P, Petrangolini G, Infantino V, Rondanelli M. 2019. Efficacy of bergamot: from anti-inflammatory and anti-oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations. Food Sci Nutr. 7(2):369–384.
   PubMed Web of Science ®Google Scholar
• Rapisarda A, Germanò MP. 2013. Chapter 2, Citrus × bergamia Risso & Poiteau botanical classification, morphology, and anatomy. In: Dugo G, Bonaccorsi I, editors. Citrus bergamia: bergamot and its Derivatives. 1st ed. Boca Raton: CRC Press. p. 9–22.
   Google Scholar
• Sharifi-Rad J, Sureda A, Tenore GC, Daglia M, Sharifi-Rad M, Valussi M, Tundis R, Sharifi-Rad M, Loizzo MR, Ademiluyi AO, et al. 2017. Biological activities of essential oils: from plant chemoecology to traditional healing systems. Molecules. 22(1):70.
   PubMed Web of Science ®Google Scholar
• Siano F, Cautela D. 2021. Assessment of free plant sterols in cold pressed Citrus essential oils. Nat Prod Res. 35(21):4078–4083.
   PubMed Web of Science ®Google Scholar
• Sicari V. 2018. Optimization of the supercritical carbon dioxide separation of bergapten from bergamot essential oil. AOAC Int. 101(1):293–297.
   Google Scholar
• Statti GA, Conforti F, Sacchetti G, Muzzoli M, Agrimonti C, Menichini F. 2004. Chemical and biological diversity of Bergamot (Citrus bergamia) in relation to environmental factors. Fitoterapia. 75(2):212–216.
   PubMed Web of Science ®Google Scholar
• Thuy TT, Huong NTT, Nhung LTH, Ninh PT, Delfino DV, van Sung T. 2013. Isolation, characterisation and biological evaluation of a phenoxazine, a natural dyestuff isolated from leaves of Peristrophe bivalvis. Nat Prod Res. 27(8):771–774.
   PubMed Web of Science ®Google Scholar
• Toth PP, Patti AM, Nikolic D, Giglio RV, Castellino G, Biancucci T, Geraci F, David S, Montalto G, Rizvi A, et al. 2015. Bergamot reduces plasma lipids, atherogenic small dense LDL, and subclinical atherosclerosis in subjects with moderate hypercholesterolemia: a 6 months prospective study. Front Pharmacol. 6:299.
   PubMed Web of Science ®Google Scholar
• Verzera A, Trozzi A, Gazea F, Cicciarello G, Cotroneo A. 2003. Effects of rootstock on the composition of bergamot (Citrus bergamia Risso et Poiteau) essential oil. J Agric Food Chem. 51(1):206–210.
   PubMed Web of Science ®Google Scholar
• Visalli G, Ferlazzo N, Cirmi S, Campiglia P, Gangemi S, Di Pietro A, Calapai G, Navarra M. 2014. Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells. Anticancer Agents Med Chem. 14(10):1402–1413.
   PubMed Web of Science ®Google Scholar
• Wang J, Zhu Y, Shi J, Yan H, Wang M, Ma W, Zhang Y, Peng Q, Chen Y, Lin Z. 2020. Discrimination and identification of aroma profiles and characterized odorants in Citrus blend black tea with different Citrus species. Molecules. 25(18):4208.
   PubMed Web of Science ®Google Scholar
• Watanabe E, Kuchta K, Kimura M, Rauwald HW, Kamei T, Imanishi J. 2015. Effects of bergamot (Citrus bergamia (Risso) Wright & Arn.) essential oil aromatherapy on mood states, parasympathetic nervous system activity, and salivary cortisol levels in 41 healthy females. Forsch Komplementmed. 22(1):43–49.
   PubMedGoogle Scholar
• Zhou Y, Wang J, Yang W, Qi X, Lan L, Luo L, Yin Z. 2017. Bergapten prevents lipopolysaccharide-induced inflammation in RAW264.7 cells through suppressing JAK/STAT activation and ROS production and increases the survival rate of mice after LPS challenge. Int Immunopharmacol. 48:159–168.
   PubMed Web of Science ®Google Scholar